Medical Device Daily Senior
Surgeons today reconnect severed blood vessels the same way they did 100 years ago - with a needle and thread. The method earned French surgeon Alexis Carrel a Nobel Prize in 1912, but at last there may be a better way - without using sutures.
Led by microsurgeon Geoffrey Gurtner, MD, a team of researchers at Stanford University School of Medicine (Stanford, California) have used a poloxamer gel and bioadhesive instead of sutures to fuse blood vessels together in animals. Results of their research were published online this week in Nature Medicine.
Gurtner told Medical Device Daily that his team had not presented the research very extensively so not a lot of people in the medical field were aware of it until it was published on Monday. Since then, he said he has received “several hundred emails“ from surgeons in a variety of specialities including urology, reproduction, and neurology, who are interested in using this technique for their unique connection problems. He said the reaction has been “surprising.“
“You work on something for four years and you feel like you're in an echo chamber and nobody is paying attention,“ Gurtner said. “It's nice that this seems to resonate with people who are working out in the trenches.“
The trouble with using sutures is that they are difficult to use on blood vessels less than 1 millimeter wide. Gurtner said he began thinking about alternatives to the needle-and-thread method about 10 years ago when he was chief of microsurgery at Bellevue (New York). “We had an infant — 10 to 12 months old — who had a finger amputated by the spinning wheel of an indoor exercise bike,“ said Gurtner, senior author of the study and professor of surgery. “We struggled with reattaching the digit because the blood vessels were so small — maybe half a millimeter. The surgery took more than five hours, and at the end we were only able to get in three sutures. Everything turned out okay in that case, but what struck me was how the whole paradigm of sewing with a needle and thread kind of falls apart at that level of smallness.“
Using sutures also can lead to complications, such as intimal hyperplasia, in which cells respond to the trauma of the needle and thread by proliferating on the inside wall of the blood vessel, causing it to narrow at that point. This increases the risk of a blood clot getting stuck and obstructing blood flow. In addition, sutures may trigger an immune response, leading to inflamed tissue that also increases the risk of a blockage.
The Stanford researchers say the new method could sidestep these problems. “Ultimately, this has the potential to improve patient care by decreasing amputations, strokes and heart attacks while reducing healthcare costs,“ the authors wrote.
Earlier in his career, as Gurtner contemplated a better way of joining together blood vessels, he considered whether ice could be used to fill the lumen, the inner space of the blood vessel, to keep both ends open to their full diameter long enough to glue them together. The idea didn't pan out so well though. “Water turns to ice quite slowly and you would have to drop the temperature of the surgical site a lot — from 98.6 degrees to 32 degrees Fahrenheit,“ he said.
Shortly after arriving at Stanford in 2005, Gurtner approached fellow faculty member Gerald Fuller, PhD, a professor of chemical engineering, about whether he knew of a substance that could be turned easily from a liquid to a solid and back to a liquid again, and that would also be safe to use in vascular surgery. Fuller suggested a FDA-approved thermoreversible poloxamer called Poloxamer 407. It is constructed of polymer blocks whose properties can be reversed by heating.
Fuller teamed up with Jayakumar Rajadas, PhD, director of the Stanford Biomaterials and Advanced Drug Delivery Laboratory, to modify the poloxamer so that it would become solid and elastic when heated above body temperature but dissolve harmlessly into the bloodstream when cooled. The poloxamer then was used to distend both openings of a severed blood vessel, allowing researchers to glue them together precisely.
“This was a collaboration between chemical engineers and clinical surgeons and biologists so it was really a team effort and a lot of people were involved,“ Gurtner said. “Without having the right team I could never get going or get step one done . . . in the five years I've been out here we've made quantum leaps forward.“
The Stanford team used a simple halogen lamp to heat the gel. In tests on animals, the technique was found to be five times faster than the traditional hand-sewn method, according to the study authors. It also resulted in considerably less inflammation and scarring after two years. The method even worked on extremely slim blood vessels — those only 0.2 mm wide — which would have been too tiny and delicate for sutures. “That's where it really shines,“ Gurtner said.
Dermabond, a surgical sealant made by Johnson & Johnson (New Brunswick, New Jersey), was used to attach the ends of the blood vessels together.
Gurtner told MDD the biggest challenge the team faced — and continues to face — is finding a glue that works and is able to set up quickly enough and be compatible with the blood vessel walls and have sufficient strength to withstand arterial pressure. “We have very demanding specifications for this glue and the glue is really kind of the weak link in this technology,“ Gurtner said. He said the Dermabond glue used in the study was okay but not the one the team plans to take to the clinic for a variety of reasons, primarily the fact that it takes too long to dry.
Once the researchers find the right glue, they will be ready to seek permission from the FDA to start a clinical trial. “That's the last piece in the puzzle. We've already thought about what the trial would look like and where we would do it at,“ he said.
Poloxamers have been used before as a vehicle for delivering drugs, including chemotherapeutics, vaccines and anti-viral therapies. Researchers have used Poloxamer 407 to occlude blood vessels in experimental animals for the purpose of evaluating the gel's safety and efficacy in so-called “beating heart surgery,“ in which certain vessels need to be temporarily blocked to improve visibility for the surgeons performing a coronary artery bypass.
Although other sutureless methods have been developed, they generally have not produced better outcomes, the authors said. “Often, the use of microclips, staples or magnets is itself traumatic to blood vessels leading to failure rates comparable to or higher than sutured anastomoses,“ they wrote.
The study authors say further testing on large animals is needed before human trials can begin, but they note that all of the components used in the technique are already approved by the FDA.
Michael Longaker, MD, the Deane P. and Louise Mitchell Professor in the School of Medicine and a co-author of the study, called the technique a “potential game-changer.“
“When you're bringing together hollow tubes, whether they're large structures, like the colon or the aorta, or a small structure, like a vein in the finger of a child, you're always worried about lining them up directly and effectively sealing them,“ Longaker said. “The technique that Dr. Gurtner has pioneered could allow surgeons to perform anastomosis more quickly and with improved precision. Coming up with this solution was the result of the classic Stanford model of bringing together researchers from a variety of disciplines.“
Amanda Pedersen, 912-660-2282